Oxysterols derived from cholesterol (WP4545)

Homo sapiens

Open in new tab Open in NDEx

Download PNG Download SVG Download JSON Download GPML Learn more about Downloads

Authors

Activity

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Communities

Annotations

Disease Ontology

Cell Type Ontology

Pathway Ontology

References

1. Cloning and regulation of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis. Jelinek DF, Andersson S, Slaughter CA, Russell DW. J Biol Chem. 1990 May 15;265(14):8190–7. PubMed Europe PMC Scholia
2. Molecular cloning and sequence analysis of cDNA encoding human cholesterol 7 alpha-hydroxylase. Noshiro M, Okuda K. FEBS Lett. 1990 Jul 30;268(1):137–40. PubMed Europe PMC Scholia
3. 7 alpha hydroxylation of 25-hydroxycholesterol in liver microsomes. Evidence that the enzyme involved is different from cholesterol 7 alpha-hydroxylase. Toll A, Wikvall K, Sudjana-Sugiaman E, Kondo KH, Björkhem I. Eur J Biochem. 1994 Sep 1;224(2):309–16. PubMed Europe PMC Scholia
4. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, et al. J Biol Chem. 1997 Feb 7;272(6):3137–40. PubMed Europe PMC Scholia
5. Markedly reduced bile acid synthesis but maintained levels of cholesterol and vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene. Rosen H, Reshef A, Maeda N, Lippoldt A, Shpizen S, Triger L, et al. J Biol Chem. 1998 Jun 12;273(24):14805–12. PubMed Europe PMC Scholia
6. Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways. Pikuleva IA, Babiker A, Waterman MR, Björkhem I. J Biol Chem. 1998 Jul 17;273(29):18153–60. PubMed Europe PMC Scholia
7. cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism. Lund EG, Kerr TA, Sakai J, Li WP, Russell DW. J Biol Chem. 1998 Dec 18;273(51):34316–27. PubMed Europe PMC Scholia
8. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Lund EG, Guileyardo JM, Russell DW. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7238–43. PubMed Europe PMC Scholia
9. Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1. Wu Z, Martin KO, Javitt NB, Chiang JY. J Lipid Res. 1999 Dec;40(12):2195–203. PubMed Europe PMC Scholia
10. RORgammaT, a thymus-specific isoform of the orphan nuclear receptor RORgamma / TOR, is up-regulated by signaling through the pre-T cell receptor and binds to the TEA promoter. Villey I, de Chasseval R, de Villartay JP. Eur J Immunol. 1999 Dec;29(12):4072–80. PubMed Europe PMC Scholia
11. Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Ferdinandusse S, Denis S, Clayton PT, Graham A, Rees JE, Allen JT, et al. Nat Genet. 2000 Feb;24(2):188–91. PubMed Europe PMC Scholia
12. Expression cloning of an oxysterol 7alpha-hydroxylase selective for 24-hydroxycholesterol. Li-Hawkins J, Lund EG, Bronson AD, Russell DW. J Biol Chem. 2000 Jun 2;275(22):16543–9. PubMed Europe PMC Scholia
13. Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase. Jones JM, Gould SJ. Biochem Biophys Res Commun. 2000 Aug 18;275(1):233–40. PubMed Europe PMC Scholia
14. 24-hydroxycholesterol is a substrate for hepatic cholesterol 7alpha-hydroxylase (CYP7A). Norlin M, Toll A, Björkhem I, Wikvall K. J Lipid Res. 2000 Oct;41(10):1629–39. PubMed Europe PMC Scholia
15. Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha. Song C, Liao S. Endocrinology. 2000 Nov;141(11):4180–4. PubMed Europe PMC Scholia
16. Characterization of an acyl-coA thioesterase that functions as a major regulator of peroxisomal lipid metabolism. Hunt MC, Solaas K, Kase BF, Alexson SEH. J Biol Chem. 2002 Jan 11;277(2):1128–38. PubMed Europe PMC Scholia
17. Metabolism of 4 beta -hydroxycholesterol in humans. Bodin K, Andersson U, Rystedt E, Ellis E, Norlin M, Pikuleva I, et al. J Biol Chem. 2002 Aug 30;277(35):31534–40. PubMed Europe PMC Scholia
18. The enzymes, regulation, and genetics of bile acid synthesis. Russell DW. Annu Rev Biochem. 2003;72:137–74. PubMed Europe PMC Scholia
19. Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol clearance. Dussault I, Yoo HD, Lin M, Wang E, Fan M, Batta AK, et al. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):833–8. PubMed Europe PMC Scholia
20. Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease. Cheng JB, Jacquemin E, Gerhardt M, Nazer H, Cresteil D, Heubi JE, et al. J Clin Endocrinol Metab. 2003 Apr;88(4):1833–41. PubMed Europe PMC Scholia
21. Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Mast N, Norcross R, Andersson U, Shou M, Nakayama K, Bjorkhem I, et al. Biochemistry. 2003 Dec 9;42(48):14284–92. PubMed Europe PMC Scholia
22. Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis. Ferdinandusse S, Ylianttila MS, Gloerich J, Koski MK, Oostheim W, Waterham HR, et al. Am J Hum Genet. 2006 Jan;78(1):112–24. PubMed Europe PMC Scholia
23. Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy. Ferdinandusse S, Kostopoulos P, Denis S, Rusch H, Overmars H, Dillmann U, et al. Am J Hum Genet. 2006 Jun;78(6):1046–52. PubMed Europe PMC Scholia
24. Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs. Hunt MC, Rautanen A, Westin MAK, Svensson LT, Alexson SEH. FASEB J. 2006 Sep;20(11):1855–64. PubMed Europe PMC Scholia
25. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig. Radhakrishnan A, Ikeda Y, Kwon HJ, Brown MS, Goldstein JL. Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6511–8. PubMed Europe PMC Scholia
26. 27-hydroxycholesterol is an endogenous selective estrogen receptor modulator. DuSell CD, Umetani M, Shaul PW, Mangelsdorf DJ, McDonnell DP. Mol Endocrinol. 2008 Jan;22(1):65–77. PubMed Europe PMC Scholia
27. 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Umetani M, Domoto H, Gormley AK, Yuhanna IS, Cummins CL, Javitt NB, et al. Nat Med. 2007 Oct;13(10):1185–92. PubMed Europe PMC Scholia
28. Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Mast N, White MA, Bjorkhem I, Johnson EF, Stout CD, Pikuleva IA. Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9546–51. PubMed Europe PMC Scholia
29. Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide. Diczfalusy U, Olofsson KE, Carlsson AM, Gong M, Golenbock DT, Rooyackers O, et al. J Lipid Res. 2009 Nov;50(11):2258–64. PubMed Europe PMC Scholia
30. 25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production. Bauman DR, Bitmansour AD, McDonald JG, Thompson BM, Liang G, Russell DW. Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16764–9. PubMed Europe PMC Scholia
31. Cerebrospinal fluid steroidomics: are bioactive bile acids present in brain? Ogundare M, Theofilopoulos S, Lockhart A, Hall LJ, Arenas E, Sjövall J, et al. J Biol Chem. 2010 Feb 12;285(7):4666–79. PubMed Europe PMC Scholia
32. Identification and pharmacological characterization of cholesterol-5,6-epoxide hydrolase as a target for tamoxifen and AEBS ligands. de Medina P, Paillasse MR, Segala G, Poirot M, Silvente-Poirot S. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13520–5. PubMed Europe PMC Scholia
33. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Porter FD, Scherrer DE, Lanier MH, Langmade SJ, Molugu V, Gale SE, et al. Sci Transl Med. 2010 Nov 3;2(56):56ra81. PubMed Europe PMC Scholia
34. Disorders of bile acid synthesis. Clayton PT. J Inherit Metab Dis. 2011 Jun;34(3):593–604. PubMed Europe PMC Scholia
35. Cholesterol 25-hydroxylation activity of CYP3A. Honda A, Miyazaki T, Ikegami T, Iwamoto J, Maeda T, Hirayama T, et al. J Lipid Res. 2011 Aug;52(8):1509–16. PubMed Europe PMC Scholia
36. Oxysterols direct B-cell migration through EBI2. Liu C, Yang XV, Wu J, Kuei C, Mani NS, Zhang L, et al. Nature. 2011 Jul 27;475(7357):519–23. PubMed Europe PMC Scholia
37. Oxysterols direct immune cell migration via EBI2. Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D, Pereira JP, et al. Nature. 2011 Jul 27;475(7357):524–7. PubMed Europe PMC Scholia
38. Role of a disordered steroid metabolome in the elucidation of sterol and steroid biosynthesis. Shackleton CHL. Lipids. 2012 Jan;47(1):1–12. PubMed Europe PMC Scholia
39. 27-Hydroxycholesterol, does it exist? On the nomenclature and stereochemistry of 26-hydroxylated sterols. Fakheri RJ, Javitt NB. Steroids. 2012 May;77(6):575–7. PubMed Europe PMC Scholia
40. The emerging role of acyl-CoA thioesterases and acyltransferases in regulating peroxisomal lipid metabolism. Hunt MC, Siponen MI, Alexson SEH. Biochim Biophys Acta. 2012 Sep;1822(9):1397–410. PubMed Europe PMC Scholia
41. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Blanc M, Hsieh WY, Robertson KA, Kropp KA, Forster T, Shui G, et al. Immunity. 2013 Jan 24;38(1):106–18. PubMed Europe PMC Scholia
42. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Setchell KDR, Heubi JE, Shah S, Lavine JE, Suskind D, Al-Edreesi M, et al. Gastroenterology. 2013 May;144(5):945-955.e6; quiz e14-5. PubMed Europe PMC Scholia
43. Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties. de Medina P, Paillasse MR, Segala G, Voisin M, Mhamdi L, Dalenc F, et al. Nat Commun. 2013;4:1840. PubMed Europe PMC Scholia
44. Cerebrotendinous xanthomatosis. Björkhem I. Curr Opin Lipidol. 2013 Aug;24(4):283–7. PubMed Europe PMC Scholia
45. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Nelson ER, Wardell SE, Jasper JS, Park S, Suchindran S, Howe MK, et al. Science. 2013 Nov 29;342(6162):1094–8. PubMed Europe PMC Scholia
46. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, et al. Mol Cell Proteomics. 2014 Feb;13(2):397–406. PubMed Europe PMC Scholia
47. Human steroid and oxysterol 7α-hydroxylase CYP7B1: substrate specificity, azole binding and misfolding of clinically relevant mutants. Yantsevich AV, Dichenko YV, Mackenzie F, Mukha DV, Baranovsky AV, Gilep AA, et al. FEBS J. 2014 Mar;281(6):1700–13. PubMed Europe PMC Scholia
48. Role of AMACR (α-methylacyl-CoA racemase) and MFE-1 (peroxisomal multifunctional enzyme-1) in bile acid synthesis in mice. Autio KJ, Schmitz W, Nair RR, Selkälä EM, Sormunen RT, Miinalainen IJ, et al. Biochem J. 2014 Jul 1;461(1):125–35. PubMed Europe PMC Scholia
49. Oxysterols are agonist ligands of RORγt and drive Th17 cell differentiation. Soroosh P, Wu J, Xue X, Song J, Sutton SW, Sablad M, et al. Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12163–8. PubMed Europe PMC Scholia
50. Inflammation. 25-Hydroxycholesterol suppresses interleukin-1-driven inflammation downstream of type I interferon. Reboldi A, Dang EV, McDonald JG, Liang G, Russell DW, Cyster JG. Science. 2014 Aug 8;345(6197):679–84. PubMed Europe PMC Scholia
51. Cholestenoic acids regulate motor neuron survival via liver X receptors. Theofilopoulos S, Griffiths WJ, Crick PJ, Yang S, Meljon A, Ogundare M, et al. J Clin Invest. 2014 Nov;124(11):4829–42. PubMed Europe PMC Scholia
52. LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases. Klinke G, Rohrbach M, Giugliani R, Burda P, Baumgartner MR, Tran C, et al. Clin Biochem. 2015 Jun;48(9):596–602. PubMed Europe PMC Scholia
53. Current trends in oxysterol research. Griffiths WJ, Abdel-Khalik J, Hearn T, Yutuc E, Morgan AH, Wang Y. Biochem Soc Trans. 2016 Apr 15;44(2):652–8. PubMed Europe PMC Scholia
54. ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment. Vilarinho S, Sari S, Mazzacuva F, Bilgüvar K, Esendagli-Yilmaz G, Jain D, et al. Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):11289–93. PubMed Europe PMC Scholia
55. Bile acid analysis in human disorders of bile acid biosynthesis. Vaz FM, Ferdinandusse S. Mol Aspects Med. 2017 Aug;56:10–24. PubMed Europe PMC Scholia
56. 27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator. He S, Nelson ER. Maturitas. 2017 Oct;104:29–35. PubMed Europe PMC Scholia
57. Identification of 7α,24-dihydroxy-3-oxocholest-4-en-26-oic and 7α,25-dihydroxy-3-oxocholest-4-en-26-oic acids in human cerebrospinal fluid and plasma. Abdel-Khalik J, Crick PJ, Yutuc E, DeBarber AE, Duell PB, Steiner RD, et al. Biochimie. 2018 Oct;153:86–98. PubMed Europe PMC Scholia
58. Additional pathways of sterol metabolism: Evidence from analysis of Cyp27a1-/- mouse brain and plasma. Griffiths WJ, Crick PJ, Meljon A, Theofilopoulos S, Abdel-Khalik J, Yutuc E, et al. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Feb;1864(2):191–211. PubMed Europe PMC Scholia
59. Concentrations of bile acid precursors in cerebrospinal fluid of Alzheimer’s disease patients. Griffiths WJ, Abdel-Khalik J, Yutuc E, Roman G, Warner M, Gustafsson JÅ, et al. Free Radic Biol Med. 2019 Apr;134:42–52. PubMed Europe PMC Scholia
60. Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders. Griffiths WJ, Yutuc E, Abdel-Khalik J, Crick PJ, Hearn T, Dickson A, et al. Free Radic Biol Med. 2019 Nov 20;144:124–33. PubMed Europe PMC Scholia
61. Oxysterols as lipid mediators: Their biosynthetic genes, enzymes and metabolites. Griffiths WJ, Wang Y. Prostaglandins Other Lipid Mediat. 2020 Apr;147:106381. PubMed Europe PMC Scholia
62. The 5,6-epoxycholesterol metabolic pathway in breast cancer: Emergence of new pharmacological targets. de Medina P, Diallo K, Huc-Claustre E, Attia M, Soulès R, Silvente-Poirot S, et al. Br J Pharmacol. 2021 Aug;178(16):3248–60. PubMed Europe PMC Scholia
63. Bile acid biosynthesis in Smith-Lemli-Opitz syndrome bypassing cholesterol: Potential importance of pathway intermediates. Abdel-Khalik J, Hearn T, Dickson AL, Crick PJ, Yutuc E, Austin-Muttitt K, et al. J Steroid Biochem Mol Biol. 2021 Feb;206:105794. PubMed Europe PMC Scholia